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STI571 (Glivec®) affects histamine release and intracellular pH after alkalinisation in HMC‐1 560, 816
Author(s) -
Löber Kristin,
Alfonso Amparo,
Escribano Luis,
Botana Luis M.
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21458
Subject(s) - ionomycin , histamine , exocytosis , intracellular , chemistry , protein kinase c , cytosol , microbiology and biotechnology , endocrinology , medicine , biology , biochemistry , signal transduction , secretion , enzyme
The human mast cell line (HMC‐1 560, 816 ) was used to study the effect of the tyrosine kinase inhibitor STI571 (Glivec®) on exocytosis, intracellular Ca 2+ and pH changes, because STI571 inhibits the proliferation of HMC‐1 560 and induces its apoptosis. This drug does not have these effects on HMC‐1 560, 816 . Exocytosis in HMC‐1 560, 816 cells can be stimulated by alkalinisation with NH 4 Cl as well as with ionomycin. Surprisingly 24‐h pre‐incubation with STI571 decreases spontaneous histamine release of HMC‐1 560, 816 cells, but increases the histamine response after alkalinisation and not after ionomycin‐stimulation. After addition of NH 4 Cl, pH i has a higher increase in STI571 pre‐incubated cells, without changing intracellular Ca 2+ concentration. Activation of PKC in combination with tyrosine kinase inhibition increases also histamine release in HMC‐1 560, 816 cells. Strangely, STI571 pre‐incubated cells with PKC inhibited by rottlerin show the same effects. In these cells, cytosolic pH increases more than in control cells. This is the first report of STI571 effect in HMC‐1 560, 816 cells. It seems that different pathways modulate signals for proliferation and exocytosis. STI571 does not only inhibit KIT TyrK, but may also influence cytosolic pH after alkalinisation in both cell lines, HMC‐1 560 and HMC‐1 560, 816 , and this ends in induced histamine release. This work is important since HMC‐1 560, 816 cells are reported in 80% of aggressive systemic mastocytosis cases and the understanding of some signalling pathways involved in mast cell response could facilitate drug targeting. J. Cell. Biochem. 103: 865–876, 2008. © 2007 Wiley‐Liss, Inc.